Anemia, and Urinary incontinence

Acute intermittent porphyria is the most frequent and the most severe form of the acute hepatic porphyrias (see this term). It is characterized by the occurrence of neuro-visceral attacks without cutaneous manifestations.

ACUTE INTERMITTENT PORPHYRIA Is also known as ups deficiency|porphyria, swedish type|pbgd deficiency|porphobilinogen deaminase deficiency|uroporphyrinogen synthase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Muscle weakness
• Pain

SOURCES: OMIM ORPHANET MESH MENDELIAN

Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase (MUT ) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR ). Different forms of the disorder have been classified according to complementation groups of cells in vitro: cblC, cblD (OMIM ), cblF (OMIM ), and cblJ (OMIM ).Isolated methylmalonic acidurias have also been classified by complementation groups: MMA 'mut' (OMIM ) is caused by mutation in the MUT gene on chromosome 6p21; MMA cblA (OMIM ) is caused by mutation in the MMAA gene (OMIM ) on 4q31; and MMA cblB (OMIM ) is caused by mutation in the MMAB gene (OMIM ) on 12q24.Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of vitamin B12 (cobalamin) metabolism, with about 250 known cases (Lerner-Ellis et al., 2006). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood (Rosenblatt et al., 1997).

METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLC TYPE; MAHCC Is also known as vitamin b12 metabolic defect with combined deficiency of methylmalonyl-coa mutase and homocysteine:methyltetrahydrofolate methyltransferase|methylmalonic aciduria and homocystinuria, vitamin b12-responsive|methylmalonic acidemia and homocystinuria, cblc t

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.

FABRY DISEASE Is also known as ceramide trihexosidase deficiency|hereditary dystopic lipidosis|fd|alpha-galactosidase a deficiency|diffuse angiokeratoma|gla deficiency|angiokeratoma corporis diffusum|anderson-fabry disease

• Seizures
• Short stature
• Hearing impairment
• Sensorineural hearing impairment
• Pain

SOURCES: ORPHANET OMIM MESH MENDELIAN

Posterior column ataxia - retinitis pigmentosa is characterized by the association of progressive sensory ataxia and retinitis pigmentosa.

POSTERIOR COLUMN ATAXIA-RETINITIS PIGMENTOSA SYNDROME Is also known as pcarp|autosomal recessive posterior column ataxia and retinitis pigmentosa

• Intellectual disability
• Seizures
• Generalized hypotonia
• Scoliosis
• Ataxia

SOURCES: ORPHANET MESH OMIM MENDELIAN

McLeod neuroacanthocytosis syndrome (MLS) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens.

MCLEOD NEUROACANTHOCYTOSIS SYNDROME Is also known as mls|x-linked mcleod syndrome

• Seizures
• Short stature
• Muscle weakness
• Cognitive impairment
• Anemia

SOURCES: ORPHANET OMIM MENDELIAN

Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, severity, and cognitive involvement are variable (review by Gregory et al., 2009).Panthothenate kinase-associated neurodegeneration has been classified clinically as 'classic,' 'atypical,' or 'intermediate.' In the classic form, patients present within the first decade of life with rapidly progressing disease and loss of ambulation approximately 15 years later. In the atypical form, patients have onset in the second decade with slow progression and maintain independent ambulation after 15 years. In the intermediate form, patients have early onset and slow progression or later onset and rapid progression. Patients with early onset tend to develop pigmentary retinopathy, whereas those with later onset tend to have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI (Hayflick et al., 2003; Pellecchia et al., 2005).Kumar et al. (2006) noted that the 'eye of the tiger' sign is not pathognomonic for PANK2 mutations. They reported 2 unrelated adult patients with cognitive dysfunction who had the characteristic sign on MRI but did not have mutations in the PANK2 gene.Gregory et al. (2009) provided a detailed review of the different forms of neurodegeneration with brain iron accumulation.In addition, some patients with Kufor-Rakeb syndrome (OMIM ), also known as Parkinson disease-9 (PARK9), have iron deposition in the basal ganglia. Genetic Heterogeneity of Neurodegeneration with Brain Iron AccumulationNeurodegeneration with brain iron accumulation is an umbrella term that encompasses a group of genetically heterogeneous disorders. See also NBIA2A (OMIM ) and NBIA2B (OMIM ), both caused by mutation in the PLA2G6 gene (OMIM ); NBIA3 (OMIM ), caused by mutation in the FTL gene (OMIM ); NBIA4 (OMIM ), caused by mutation in the C19ORF12 gene (OMIM ); NBIA5 (OMIM ), caused by mutation in the WDR45 gene (OMIM ); NBIA6 (OMIM ), caused by mutation in the COASY gene (OMIM ); NBIA7 (OMIM ), caused by mutation in the REPS1 gene (OMIM ); and NBIA8 (OMIM ), caused by mutation in the CRAT gene (OMIM ).See review of Schneider and Bhatia (2012) on syndromes of neurodegeneration with brain iron accumulation, including Kufor-Rakeb disease (OMIM ) and aceruloplasminemia (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1; NBIA1 Is also known as hallervorden-spatz disease|pkan|pkan neuroaxonal dystrophy, juvenile-onset|pantothenate kinase-associated neurodegeneration

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Failure to thrive

SOURCES: OMIM ORPHANET MENDELIAN

Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by Bellus et al., 1995).

• Intellectual disability
• Short stature
• Generalized hypotonia
• Hearing impairment
• Scoliosis

SOURCES: MESH OMIM MENDELIAN

Ss blood group antigens reside on the red-cell glycoprotein GYPB. The S and s antigens result from a polymorphism at amino acid 29 of GYPB, where S has met29 and s has thr29. The U antigen refers to a short extracellular sequence in GYPB located near the membrane. GYPB, glycophorin A (GYPA ), and glycophorin E (GYPE ) are closely linked on chromosome 4q31. Antigens of the MN blood group (OMIM ) reside on GYPA. The M and N antigens differ at amino acids 1 and 5 of GYPA, where M is ser-ser-thr-thr-gly, and N is leu-ser-thr-thr-glu. The N terminus of GYPB is essentially identical to that of GYPA except that it always expresses the N antigen, denoted 'N' or N-prime. Recombination and gene conversion between GYPA, GYPB, and GYPE lead to hybrid glycophorin molecules and generation of low-incidence antigens. Thus, the MN and Ss blood groups are together referred to as the MNSs blood group system (see {111300}). Recombination results in 3 glycophorin-null phenotypes: En(a-) cells lack GYPA due to recombination between GYPA and GYPB; GYPB-negative (S-s-U-) cells lack GYPB due to recombination in GYPB; and M(k) cells (M-N-S-s-U-) lack both GYPA and GYPB due to recombination between GYPA and GYPE. Individuals with glycophorin-null phenotypes have decreased sialic acid content and increased resistance to malarial infection (see {611162}). GYPA and GYPB are not essential for red-cell development or survival, and GYPA- and GYPB-null phenotypes are not associated with anemia or altered red-cell function (review by Cooling, 2015).

BLOOD GROUP, SS; SS Is also known as ss blood group

• Neoplasm
• Anemia

SOURCES: OMIM MENDELIAN

SICKLE CELL-HEMOGLOBIN C DISEASE SYNDROME Is also known as hbsc disease

• Pain
• Anemia
• Fatigue

SOURCES: ORPHANET MENDELIAN

Generalized dominant dystrophic epidermolysis bullosa (DDEB-gen) is a subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as DDEB, Pasini and Cockayne-Touraine types, characterized by generalized blistering, milia formation, atrophic scarring, and dystrophic nails.

GENERALIZED DOMINANT DYSTROPHIC EPIDERMOLYSIS BULLOSA Is also known as autosomal dominant dystrophic epidermolysis bullosa, pasini and cockayne-touraine types|ddeb, pasini and cockayne-touraine types|ddeb, generalized|ddeb-gen

• Anemia
• Dysphagia
• Carious teeth
• Abnormality of the fingernails
• Hypopigmented skin patches

SOURCES: ORPHANET MENDELIAN