Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient.

We report the case of a 10-year-old Spanish girl with mutations in NADK2 Prenatal central nervous system abnormalities showed ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum. At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy were detected. Metabolic investigations revealed high lysine, lactate, and pipecolic acid levels in blood and cerebrospinal fluid. Pyruvate carboxylase and pyruvate dehydrogenase activity in fibroblasts were normal. Beginning at birth she received biotin, thiamine, and carnitine supplementation. A lysine-restricted diet was started when she was 1 month old. Because pipecolic acid was high, pyridoxine was added to treatment. At 3 years old, astatic myoclonic epilepsy appeared, with no response to levetiracetam. We switched pyridoxine to pyridoxal phosphate, with electroclinical improvement. Because the activity of mitochondrial respiratory chain complexes III and IV was slightly low in muscle, other cofactors such as ubidecarenone, idebenone, vitamin E, and creatine were added to the treatment. At 8 years old, plasma acylcarnitine testing was performed, and high levels of 2-trans, 4-cis-decadienoylcarnitine were found. Whole exome sequencing identified a homozygous splice site mutation in NADK2 (c.956+6T>C; p.Trp319Cysfs*21). This substitution generates exon skipping, leading to a truncated protein. In fact, NADK2 messenger RNA and the corresponding protein were almost absent. Now, at 10 years of age she presents with ataxia and incoordination. She has oromotor dysphasia but is able to understand fluid language and is a very friendly girl. We hypothesize that the patient's clinical improvement could be due to her lysine-restricted diet together with cofactors and pyridoxal phosphate administration.

Acute and chronic hypoglycemic effect of Ibervillea sonorae root extracts-II.

Ibervillea sonorae's root, or "wareque" (Cucurbitaceae), is widely used in Mexican traditional medicine for the control of diabetes mellitus. In the present study, the hypoglycemic effects produced by the acute and chronic administration of various extracts of Ibervillea sonorae were investigated. Both the traditional preparation (aqueous decoction) and the raw extract (juice) from the root resulted in significant reductions of glycemia in healthy mice after intraperitoneal administration at a dose of 600 mg/kg. Additionally, ground dried root was used to obtain a dichloromethane (DCM) extract and a methanol (MeOH) extract. The DCM extract induced a clear reduction of glycemia in healthy (P < 0.05) and in alloxan-diabetic mice. The intraperitoneally administered DCM extract caused a severe hypoglycemia that produced lethality in all the treated animals when doses of 300 and 600 mg/kg body weight were used. Since the DCM extract showed a marked hypoglycemic activity, it was administered daily per os to alloxan diabetic rats, employing corn oil and tolbutamide as controls. After 41 days of DCM extract administration at a dose of 300 mg/kg/day, diabetic rats showed improvement in glycemia, body weight, triglycerides, and GPT in comparison with the diabetic control group. Total cholesterol, GOT, and uric acid blood levels were not affected.