Nystagmus, and Inflammation of the large intestine

Low match HERMANSKY-PUDLAK SYNDROME 4; HPS4

Hermansky-Pudlak syndrome-4 (HPS4) is characterized by oculocutaneous albinism in association with easy bruising or a bleeding tendency and absence of platelet dense bodies. Some patients also exhibit pulmonary fibrosis and/or granulomatous colitis (Anderson et al., 2003).For a general phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (OMIM ).

• Nystagmus
• Visual impairment
• Respiratory distress
• Reduced visual acuity
• Bruising susceptibility

SOURCES: OMIM MENDELIAN

Low match HERMANSKY-PUDLAK SYNDROME TYPE 8

HERMANSKY-PUDLAK SYNDROME TYPE 8 Is also known as hps8

• Nystagmus
• Visual impairment
• Myopia
• Recurrent infections
• Reduced visual acuity

SOURCES: ORPHANET OMIM MENDELIAN

Low match HERMANSKY-PUDLAK SYNDROME 5; HPS5

Hermansky-Pudlak syndrome-5 (HPS5) is characterized by oculocutaneous albinism, a bleeding diathesis, and lack of platelet dense bodies. HPS5 appears to be a milder form of the syndrome because the complications present in other forms of HPS, such as pulmonary fibrosis, granulomatous colitis, and neutropenia, have not been reported in HPS5 patients (Ringeisen et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (OMIM ).

• Nystagmus
• Neoplasm
• Strabismus
• Cataract
• Thrombocytopenia

SOURCES: OMIM MENDELIAN

Low match HERMANSKY-PUDLAK SYNDROME TYPE 7

HERMANSKY-PUDLAK SYNDROME TYPE 7 Is also known as hps7

• Ataxia
• Nystagmus
• Muscle weakness
• Respiratory distress
• Reduced visual acuity

SOURCES: ORPHANET OMIM MENDELIAN

Low match HERMANSKY-PUDLAK SYNDROME 6; HPS6

• Global developmental delay
• Hearing impairment
• Nystagmus
• Strabismus
• Anemia

SOURCES: OMIM MENDELIAN

Low match METHYLCOBALAMIN DEFICIENCY TYPE CBLDV1

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 (MAHCC ), cblD, cblF (MAHCF ), and cblJ (MAHCJ ).Isolated methylmalonic acidurias have also been classified by complementation groups: MMA 'mut' (OMIM ), caused by mutation in the MUT gene on chromosome 6p21; MMA cblA (OMIM ), caused by mutation in the MMAA gene (OMIM ) on 4q31; and MMA cblB (OMIM ), caused by mutation in the MMAB gene (OMIM ) on 12q24. Another form of isolated MMA (OMIM ) can be caused by defect in the transcobalamin receptor (CD320 ).

METHYLCOBALAMIN DEFICIENCY TYPE CBLDV1 Is also known as methylmalonic acidemia, cblh type, formerly|functional methionine synthase deficiency type cbldv1|methylmalonic aciduria, cblh type, formerly|methylmalonic acidemia and homocystinuria, cbld type

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Low match AUTOSOMAL RECESSIVE CEREBELLAR ATAXIA DUE TO STUB1 DEFICIENCY

Autosomal recessive cerebellar ataxia due to STUB1 deficiency is a rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been associated.

AUTOSOMAL RECESSIVE CEREBELLAR ATAXIA DUE TO STUB1 DEFICIENCY Is also known as scar16|spinocerebellar ataxia autosomal recessive type 16

• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: ORPHANET OMIM MENDELIAN

Low match HERMANSKY-PUDLAK SYNDROME 1; HPS1

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes (Oh et al., 1998). Genetic Heterogeneity of Hermansky-Pudlak SyndromeHPS2 (OMIM ) is caused by mutation in the AP3B1 gene (OMIM ) on chromosome 5q14. HPS3 (OMIM ) is caused by mutation in the HSP3 gene (OMIM ) on chromosome 3q24. HPS4 (OMIM ) is caused by mutation in the HSP4 gene (OMIM ) on chromosome 22q12. HPS5 (OMIM ) is caused by mutation in the HPS5 gene (OMIM ) on chromosome 11p14. HPS6 (OMIM ) is caused by mutation in the HPS6 gene (OMIM ) on chromosome 10q24. HPS7 (OMIM ) is caused by mutation in the DTNBP1 gene (OMIM ) on chromosome 6p22. HPS8 (OMIM ) is caused by mutation in the BLOC1S3 gene (OMIM ) on chromosome 19q13. HPS9 (OMIM ) is caused by mutation in the PLDN gene (OMIM ) on chromosome 15q21. HPS10 (OMIM ) is caused by mutation in the AP3D1 gene (OMIM ) on chromosome 19p13.

HERMANSKY-PUDLAK SYNDROME 1; HPS1 Is also known as delta storage pool disease|albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells

• Nystagmus
• Strabismus
• Cataract
• Visual impairment
• Myopia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Low match D-BIFUNCTIONAL PROTEIN DEFICIENCY

D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (OMIM ), caused by mutation in the ACOX1 gene (OMIM ) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD ), Zellweger cerebrohepatorenal syndrome (see {214100}) and neonatal adrenoleukodystrophy (NALD; see {601539}) (Watkins et al., 1995).DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1 ). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed.

D-BIFUNCTIONAL PROTEIN DEFICIENCY Is also known as peroxisomal bifunctional enzyme deficiency|dbp deficiency|17-beta-hydroxysteroid dehydrogenase iv deficiency|pbfe deficiency

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Hypertelorism

SOURCES: ORPHANET OMIM MENDELIAN

Low match PRADER-WILLI SYNDROME; PWS

Prader-Willi syndrome is characterized by diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet. It can be considered to be an autosomal dominant disorder and is caused by deletion or disruption of a gene or several genes on the proximal long arm of the paternal chromosome 15 or maternal uniparental disomy 15, because the gene(s) on the maternal chromosome(s) 15 are virtually inactive through imprinting. Horsthemke and Wagstaff (2008) provided a detailed review of the mechanisms of imprinting of the Prader-Willi/Angelman syndrome (OMIM ) region.See also the chromosome 15q11-q13 duplication syndrome (OMIM ), which shows overlapping clinical features.

PRADER-WILLI SYNDROME; PWS Is also known as prader-labhart-willi syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN