HUT (Hutterite)

Inheritance: autosomal recessive
Genes: CPT1A

CPTI deficiency
CPT1A
CPT deficiency
CPT deficiency hepatic
CPT deficiency type I

Hypoglycemia

Seizures

Coma

Hepatomegaly

Failure to thrive

Carnitine Palmitoyl Transferase I Deficiency

Clinical Characteristics

General description (for patients):  

This is a metabolic disorder usually most severe in young children.  Low blood sugar can lead to listlessness and progress to coma and even death if untreated.  Fasting increases the risk of low sugar and other severe metabolic disturbances.  The liver is often enlarged with progressive damage.  It is possible to treat this disorder with the proper diet and patients can live a normal life if proper treatment is initiated before brain damage occurs.

Medical description:  

Early diagnosis and treatment of this disorder is successful in avoiding long term neurological damage.  Inability to oxidize long-chain fatty acids can lead to severe hypoketotic hypoglycemia, seizures, and even death with onset of symptoms usually in the first years of life.  Early signs include hypotonia, lethargy and general failure to thrive.  Presentation may resemble Reye syndrome.  Fasting increases the risk of hypoglycemic episodes. Hepatomegaly with fatty degeneration and liver necrosis is often seen.  Laboratory features include elevated carnitine, elevated transaminases, plasma free fatty acids and hyperammonemia which provide useful clues.  The disorder tends to become milder with age.

Genetics:  

This is an autosomal recessive condition caused by a mutation in the CPT1A gene encoding carnitine palmitoyl transferase located on chromosome 11 (11q13).  A base substitution (2129G>A) has been found among Hutterite families in Montana and Manitoba.

Treatment:  

Avoidance of fasting and administration of medium-chain triglycerides with a low fat diet seems to be protective of the severe metabolic consequences.

Prognosis:  

If neurological damage is avoided through early detection and treatment, the prognosis is excellent.

Ancillary treatments and support:

Physical therapy and monitoring for those with neurological damage.

Specialists and specialty centers:  

Pediatrician, gastroenterologist, nutritionist,  neurologist

References:

Haworth, J.C., Demaugre, F., Booth, F.A., Dilling, L.A., Moroz, S.P., Seshia, S.S., Seargeant, L.E., and Coates, P.M.:  Atypical features of the hepatic form of carnitine palmitoyltransferase deficiency in a Hutterite family.  J. Pediat. 121: 553-557, 1992.  PubMed ID: 1403388

Prasad, C., Johnson, J.P., Bonnefont, J.P., Dilling, L.A., Innes, A.M., Haworth, J.C., Beischel, L., Thuillier, L., Prip-Fuus, C., Singal, R., Thompson, J.R.G., Prasad, A.N., Buist, N., and Greenberg, C.R.:  Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): evidence for a founder effect and results of a pilot study on a DNA-based newborn screening program.  Mol. Genet. Metab. 73: 55-63, 2001. PubMed ID: 11350183.

Prip-Buus, C., Thuillier, L., Abadi, N., Prasad, C., Dilling, L., Klasing, J., Demaugre, F., Greenberg, C.R., Haworth, J.C., Droin, V., Kadhom, N., Gobin, S., Kamoun, P., Girard, J., Bonnefont, J.-P.:  Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community.  Molec. Genet. Metab. 73: 16-54, 2001.  PubMed ID: 11350182

Olpin, S.E., Allen, J., Bonham, J.R., Clark, S., Clayton, P.T., Calvin, J., Downing, M., Ives, K., Jones, S., Manning, N.J., pollitt, R.J., Standing, S.J., and Tanner, M.S.:  Feaures of carnitine palmitoyltransferase type I deficiency.  J. Inherit.  Metab. Dis.24: 35-42, 2001.  PubMed ID: 11286380


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