Both subtypes are autosomal recessive disorders, meaning that a mutant allele must be inherited from both parents in order to cause disease.Subtype I: Neutral Lipid Storage Disease with Myopathy (NLSD-M), is caused by a mutation in the PNPLA2 gene, which reduces the normal expression orfunction of the ATGL protein. PNPLA2 is located on chromosome 11. ATGL is an enzyme involved in catabolism of triglycerides (long-term fat storage) into fatty acids (short-term fat storage) within the body In the absence of fully functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells. In the absence of functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells. Patients with NLSD-M display progressive skeletal myopathy and severe cardiomyopathy in ~40% of cases. The pathophysiology and mechanistic basis of myopathy arising from deficits is lipid metabolism is not yet known.Subtype II:  Neutral Lipid Storage Disease with Ichthyosis (NLSD-I), or Chanarin-Dorfman syndrome, is caused by a mutation in the CGI-58 protein. CGI-58 is a coactivator of ATGL, and together these proteins sustain blood lipid levels between meals.
Higher doses and prolonged use are associated with increased incidence of vitamin B12 deficiency, and some researchers recommend screening or prevention strategies. Lactic acidosis
Lactic acidosis almost never occurs with metformin exposure during routine medical care. Rates of metformin-associated lactic acidosis are about nine per 100,000 persons/year, which is similar to the background rate of lactic acidosis in the general population. A systematic review concluded no data exists to definitively link metformin to lactic acidosis.Metformin is generally safe in people with mild to moderate chronic kidney disease, with proportional reduction of metformin dose according to severity of estimated glomerular filtration rate (eGFR) and with periodic assessment of kidney function, (e.g., periodic plasma creatinine measurement). The FDA recommends avoiding the use of metformin in more severe chronic kidney disease, below the eGFR cutoff of 30 mL/minute/1.73 m2. Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. In healthy individuals, this slight excess is cleared by other mechanisms (including uptake by unimpaired kidneys), and no significant elevation in blood levels of lactate occurs. Given severely impaired kidney function, clearance of metformin and lactate is reduced, increasing levels of both, and possibly causing lactic acid buildup. Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication.