Niemann-Pick disease (see also Niemann-Pick disease, types A and B in table Some Sphingolipidoses)

Onset: Highly variable (early or late infancy, adolescence, adulthood)

Urine metabolites: None

Clinical features: Vertical gaze palsy, hepatosplenomegaly, neonatal jaundice, dysphagia, hypotonia followed by spasticity, seizures, cerebellar ataxia, dysarthria, psychomotor delay and degeneration, psychosis and behavioral problem, fetal ascites, foam cells and sea-blue histiocytes as in Niemann-Pick disease types A and B

Earlier onset associated with faster progression and shorter lifespan

Treatment:

Hematopoietic stem cell transplantation may be effective in young patients with NPC2 mutations

Type C1/Type D (257220*)

NPC1 protein

Type C2 (607625*)

Epididymal secretory protein 1 (HE1; NPC2 protein)

1. Wolman disease (620151*)

2. Cholesteryl ester storage disease (CESD; 278000*)

Lysosomal acid lipase

Onset: In Wolman disease, infancy

In CESD, variable

Urine metabolites: None

Clinical features: Growth failure; vomiting; diarrhea; steatorrhea; hepatosplenomegaly; hepatic fibrosis; pulmonary hypertension; adrenal calcification; xanthomatous changes in liver, adrenal glands, lymph nodes, bone marrow, small intestine, lungs, and thymus; hypercholesterolemia and normal to elevated plasma lipids; foam cells in marrow

In Wolman disease, death during infancy if untreated

In CESD, premature atherosclerosis

Treatment:

Cerebrotendinous xanthomatosis (cholestanol lipidosis; 213700*)

Sterol 27-hydroxylase

Onset: Adolescence

Urine metabolites: Elevated 7-alpha-hydroxylated bile alcohol

Clinical features: Juvenile cataracts, tendon and skin xanthomas, xanthelasma, fractures, atherosclerosis, dementia, spinal cord paresis, cerebellar ataxia, developmental disability, pseudobulbar paralysis, leukodystrophy, peripheral neuropathy

Treatment: Chenodeoxycholic acid, statins

Sitosterolemia (210250*, 618666*)

Microsomal HMG-CoA reductase

ABC transporter proteins

Onset: First two decades of life

Urine metabolites: None

Clinical features: Atherosclerosis, premature coronary artery disease, abnormal red blood cells, xanthomas on tendons

Treatment: Reducing intake of foods rich in plant fats

Neuronal ceroid lipofuscinosis

Onset: In infantile form, 6–12 months

In late infantile form, 2–4 years

In juvenile forms (including CLN9), 4–10 years

In adult form, 20–39 years

In variant infantile forms, 4–7 years

In progressive epilepsy form, 5–10 years

Urine metabolites: None

Clinical features: In infantile and late infantile forms, developmental delay, microcephaly, optic and cerebral atrophy, retinal degeneration, blindness, flexion contractures, hypotonia, ataxia, myoclonus, seizures, loss of speech, hyperexcitability, autofluorescence in neurons, granular osmiophilic deposits in cells, increased serum arachidonic acid, decreased linoleic acid

In juvenile and adult forms, features of above forms plus extrapyramidal signs, progressive loss of walking ability, school and behavioral difficulties

Treatment: Supportive care

Infantile form (CLN1, Santavuori-Haltia disease; 256730*)

Palmitoyl-protein thioesterase-1

Late infantile form (CLN2, Jansky-Bielschowsky disease; 204500*)

Lysosomal pepstatin-insensitive peptidase

Juvenile form (CLN3, Batten disease, Vogt-Spielmeyer disease; 204200*)

Lysosomal transmembrane CLN3 protein

Adult form (CLN4, Kufs disease; 204300*)

Palmitoyl-protein thioesterase-1

Variant late infantile form, Finnish type (CLN5; 256731*)

Lysosomal transmembrane CLN5 protein

Variant late infantile form (CLN6; 601780*)

Transmembrane CLN6 protein

Progressive epilepsy with intellectual disability (600143*)

Transmembrane CLN8 protein

CLN9 (609055*)

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